Overexpression of GNB2L1 is associated with poor prognosis in cervical cancer patients

Abstract

Background: Among women, cervical cancer (CC) is the fourth most prevalent cancer worldwide. Multiple bio-makers have been identified for tumor diagnosis and prognosis. However, no single bio-maker for CC detection exists that is both highly sensitive and specific. In this report, we explored the role of guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1) in CC progression in Uyghur women. Methods: In the present study, 132 patients with cervical squamous cell carcinoma (CSCC), 56 cases with cervical intraepithelial neoplasia (CIN) were enrolled. GNB2L1 mRNA and protein expression levels were analyzed in CSCC, CIN, and normal cervical (NC) tissues and in CC cell lines using qRT-PCR, western blot, and immunohistochemistry. Stable GNB2L1-knockdown CC cells (shGNB2L1) were also created and lipid accumulation was measured with Oil Red O staining. Additionally, changes in GNB2L1 gene copy number were investigated with qRT-PCR and sequencing. A gene regulatory network was constructed using the STRING database. Finally, patient survival was assessed with Kaplan‑Meier and log-rank tests. Results: Our results indicated that GNB2L1 mRNA and protein are overexpressed in CSCC tumor tissues when compared to CIN and NC tissues. GNB2L1 expression was associated with the degree of cell differentiation (P = 0.001), lymph node metastasis (P = 0.049), and the clinical stage (P = 0.017). Oil Red O staining showed that lipid levels were lower in shGNB2L1 cells, and that GNB2L1 DNA copy number in CC tissues (29,7200 ± 9,815.061) was significantly higher when compared to NC tissues (19,5100 ± 5,676.392 [T=-2.770, P = 0.009]). Furthermore, patients with CSCC and high GNB2L1 expression demonstrated shorter overall survival times when compared to patients with low GNB2L1 expression (P = 0.002). Multivariate analysis indicated that GNB2L1 overexpression is an indepen­dent prognostic factor in patients with CSCC. Conclusions: Overexpression of GNB2L1 may contribute to tumor progression; therefore, it is a potential prognostic biomarker for CSCC patients.